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P660 Stability of serum concentrations of infliximab and adalimumab across pregnancy in IBD

E. Flanagan*1, P. R. Gibson2, A. Ross1, O. Rosella3, S. J. Bell1

1St Vincent's Hospital, Gastroenterology, Melbourne, Australia, 2Alfred Health, Gastroenterology, Melbourne, Australia, 3Monash University Central Clinical School, Melbourne, Australia

Background

Infliximab (IFX) and adalimumab (ADA) are IgG1 anti-tumour necrosis factor (TNF) monoclonal antibodies, which are transferred across the placenta in the second and third trimesters of pregnancy. There remains a paucity of data relating to maternal serum levels in pregnancy. A small study by Seow et al.observed that IFX levels increased during pregnancy while ADA levels remained stable.1 However, the sample size and number of intra-partum samples was limited.

Methods

Female patients with IBD on ADA or IFX, and either pregnant or planning pregnancy were enrolled. Serum trough ADA and IFX were measured in each trimester and at delivery by ELISA (Q-INFLIXI and Q-ADA, Matriks Biotek, Turkey or Promonitor, Grifols, Spain).

Results

12 patients on IFX and 4 patients on ADA with at least 2 intra-partum measurements were included. The median number of levels per patient was 3 (range 2–5). Patient characteristics are shown in Table 1.

Table 1. Patient characteristics

Infliximab cohort (n = 12): Median and individual trough IFX levels were stable (Figure 1). IFX was administered 6–8 weekly at doses of 5 mg/kg (n = 10) or 10 mg/kg (n = 2). The last dose was given at a median 30 weeks gestation. All patients were in clinical remission at the time of drug levels with normal faecal calprotectin (FCP) ( < 250 μg/g).

Figure 1. Maternal infliximab levels in pregnancy—median and individual trough concentrations.

Adalimumab cohort (n = 4): intra-partum and delivery ADA concentrations appeared stable (Figure 2). Three of the patients were on ADA 40 mg fortnightly and continued the drug throughout pregnancy; Patient A, on weekly ADA, elected to cease the drug at 30 weeks gestation. Patient B was switched to adalimumab in her second trimester 12 weeks before her earliest ADA level in pregnancy. Patient C had an elevated FCP in first trimester which then normalised, while the other three patients had normal FCP in pregnancy. Patient D was in her third trimester at the latest blood draw.

Figure 2. Maternal adalimumab levels in pregnancy.

Conclusion

In patients on stable dosing of IFX or ADA and in remission during pregnancy, maternal drug levels remain stable. Further data are required to clarify the pharmacokinetics of anti-TNF in pregnancy before recommendations can be made about dosing intervals.

References

1. Seow CH, Leung Y, Vande Casteele N, et al. The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease. Aliment Pharmacol Ther 201745:1329–38.